The effects of glutathione-related genes and cigarette smoking on lung cancer short-term survival. K. Taniguchi, P. Yang, R. Marks, T. Lesnick, A. Yokomizo, J. Sloan, D. Miller, J. Jett, H. Tazelaar, E. Edell, D. Smith, W. Liu. Mayo Clinic, Rochester, MN.

   Genes encoding glutathione (GSH) synthetase and transferases could be useful in predicting lung cancer prognosis because several GSH-related metabolic enzymes could inactivate anti-cancer drugs. We hypothesize that patients with genotypes corresponding to low activity levels of GSH-related enzymes are associated with better lung cancer survival. In a pilot study, we included 313 patients diagnosed in our institution and followed up for one year. Each patient completed a baseline interview regarding cigarette smoking status and family history of cancer and other pulmonary diseases. Medical records were abstracted to obtain clinical staging, histopathology, and treatment data. One hundred and six patients were genotyped at four GSH-related loci: GSTP1, GSTM1, GSTT1, and g-GCS. The cutpoint of 40 pack-years was used for defining light/moderate vs heavy smokers in our analysis. There were 194 males (62%) and 45 never-smokers (14%). The crude one-year survival rate was 51%. For cases with early- vs late-stage at diagnosis, the survival rates were 83% and 42%, respectively. The survival rates for patients with null genotype at two of the four loci (NN) was compared to patients with a positive genotype at one or both loci (other). We found an overall higher survival rate for patients with NN (73-86%) than patients with other genotypes (59-60%). In heavy smokers, the one-year survival rate was 71-100% in NN group compared to the 65-70% rate otherwise. This disparity between contrasting genotypes among late-stage patients (who usually underwent chemotherapy) was larger than among early-stage patients (who were mainly treated by surgical resection). The survival rate among late-stage patients with NN was approximately 20% higher than patients with other genotype. Among late-stage patients who were heavy smokers, the survival rate was 43-67% for NN and 17-33% for other genotype. These preliminary data reflect a clinically significant effect although questions involving confounding influences remain. Further investigation with a larger sample is warranted.